Thyroid hormones maintain parvalbumin neuron functions in mouse neocortex

Parvalbumin-expressing (PV) GABAergic interneurons play a key role in maintaining the excitation-inhibition balance in the mammalian neocortex. Here we investigate the function of thyroid hormones in PV neurons in the mouse neocortex. To this end, Cre/loxP recombination system was used to express a dominant negative mutated receptor of thyroid hormones only in PV neurons. We analyzed the neocortical phenotype of these mice, in which thyroid hormone signaling is selectively disrupted in PV neurons, by combining genomics, histology, electrophysiology, sleep recordings and behavioral analysis. In the mutant mice, gene expression analysis revealed a decreased expression of key perineuronal net components of PV neurons. PV neuron excitability was decreased, leading to behavioral hyperactivity and increased susceptibility to seizures. Additionally, sleep analysis revealed that mutant mice spent more time awake, and a delayed transition to sleep, suggesting impairments in sleep regulation mechanisms. Electrophysiological recordings further demonstrated altered gamma oscillations in the somatosensory cortex. These results highlight that thyroid hormones are not only required for the differentiation of PV interneurons, but also for the maintenance of their inhibitory function after the onset of parvalbumin expression.